Abstract

Our aim was to investigate whether there is a season-of-birth effect in
anorexia nervosa. In a meta-analysis, we compared the distribution of anorexia
births (n = 1293) from four independent UK cohorts to that of the general UK
population (n = 21 914 037), using both the Walter & Elwood seasonality
and chi-squared tests. We found an excess of anorexia births from March to
June (odds ratio (OR) = 1.15, 95% CI 1.03–1.29, P = 0.012) and a deficit
from September to October (OR = 0.8, 95% CI 0.68–0.94, P = 0.007). These
results indicate that environmental risk factor(s) are operative during
gestation or immediately after birth and their identification will be
important for disease prevention strategies.

A growing body of evidence suggests a role for season of birth in
determining susceptibility to a wide range of psychiatric disorders such as
schizophrenia, bipolar disorder, major depression and suicidal
behaviour.1,
2
This hypothesis has been investigated in people with anorexia nervosa and
other eating
disorders;3–
8
however, although an excess of spring births has been suggested, results are
conflicting and rarely achieve statistical significance. The reasons for this
conflict are at least twofold. First, season-of-birth studies require a large
number of cases to achieve sufficient statistical power to detect small
differences in seasonal births between patients and controls. However, these
studies only looked at a few hundred people with anorexia, resulting in less
than 30% power to detect the presence of a seasonal risk factor with an odds
ratio of 1.2. Second, differences in the statistical tests used may provide
another explanation for conflicting results. Standard techniques such as a
simple chi-squared tests (used in most of the previous studies on anorexia)
are easy to perform but non-standard techniques such as harmonic and spectral
analysis are more powerful and suitable for this type of
investigation.9 We
therefore performed a meta-analysis on four UK cohorts of individuals with
anorexia nervosa, making this the largest study to assess the presence of a
season-of-birth effect in anorexia.

Method

The PubMed database was searched using the search strings “anorexia
nervosa AND season”, “anorexia AND month” and “
anorexia AND birth” to identify relevant articles. Given the
potential confounding role of country-specific factors such as different
social and nutritional habits, disease prevalence, birth trends and latitude,
we decided to include only studies from the UK. Online Table DS1 shows the
main features and findings of the studies included in the meta-analysis.

A pooled total of 1293 anorexia nervosa births were compared with those of
the general population born between 1950 and 1980 (n = 21 914 037)
obtained from the UK Office for National Statistics
(www.statistics.gov.uk/).
This birth interval (1950–1980) matches that of the individuals with
anorexia. To assess the presence of a month-of-birth effect in anorexia
nervosa, we used both the Walter & Elwood’s
seasonality10 and
chi-squared tests. With the Walter & Elwood’s seasonality test it is
possible to estimate within-year fluctuations with a 12-month periodicity
(simple harmonic seasonal variation). Our study had a power of 80% to detect
the presence of a seasonal factor with an odds ratio (OR) of 1.2.

Results

The monthly distributions of anorexia births and general population births
across the year are shown in
Fig.
1. Using the Walter & Elwood’s test, the birth
distribution of those in the anorexia nervosa group was found to be
significantly different from that of the general population (P =
0.02). To confirm these findings we performed a chi-squared analysis.
Similarly, the birth distribution of those in the anorexia nervosa group
significantly differed from that of the general population, being higher in
the first half of the year compared with the second half (OR = 1.13, 95% CI
1.01–1.26, P = 0.025). Further analyses highlighted an excess
of anorexia nervosa births from March to June (OR = 1.15, 95% CI
1.03–1.29, P = 0.012) and a deficit from September to October
(OR = 0.8, 95% CI 0.68–0.94, P = 0.007) in comparison with the
rest of the year. The peak-to-trough ratio was then evaluated comparing the
periods March–June with September–October (OR = 1.31, 95% CI
1.1–1.56, P = 0.001).

Percentage distribution of births in individuals with anorexia and the
general population.

Discussion

In line with the ‘fetal origin of adult disease’ hypothesis,
formulated by David Barker, it is now acknowledged that early-life exposure to
environmental factors may influence the risk of late-onset
diseases.11 Here we
provide clear evidence in support of a season-of-birth effect in anorexia
nervosa. A number of studies have shown such an effect in psychiatric
disorders. Thus, the presence of similar findings in anorexia is perhaps not
surprising. By using a large sample size of people with anorexia nervosa and
controls and adopting both standard (chi-squared) and non-standard (Walter & Elwood) statistical approaches, we were able to confirm more confidently
what other studies had previously only suggested. Consistent with our
findings, an excess of anorexia and bulimia nervosa births during the spring
was observed in other studies, raising the possibility that the same factor(s)
could also influence susceptibility to other eating disorders. However, small
sample sizes, inappropriate statistical methodologies and conflicting results
did not allow any definite
conclusion.8
Intriguingly, a similar excess of spring births has also been observed in
major depression, perhaps suggesting the presence of shared environmental risk
factors acting early in
life.2 Also of
interest is a recent study reporting an interaction between the D4
dopamine receptor gene and season of birth influencing body weight regulation
in women with bulimia
nervosa.12

It is important to understand that the season-of-birth effect can be
considered as a marker of several environmental agents influencing disease
risk. The excess of spring births could be the consequence of environmental
factor(s) acting at any time from conception to the first postnatal months.
Thus, the identification of the relevant factors remains a challenging goal.
However, seasonal changes in temperature, sunlight exposure and consequent
vitamin D levels, maternal nutrition and infections are all strong candidate
factors. Intriguingly, vitamin D levels have been shown to be associated with
psychiatric
disorders.13
Although the presence of low vitamin D levels in people with psychiatric
illness may be the consequence of reverse causation, further support for a
role for vitamin D comes from functional studies showing that it is also
involved in neuroprotection and brain
development.14,
15

To conclude, using the largest cohort of people with anorexia to date, we
demonstrated that susceptibility to anorexia nervosa is significantly
influenced by the season of birth, with higher rates in those individuals born
in the spring and lower ones in those born in the autumn. Future studies with
even larger sample sizes in different populations and at different latitudes
are needed to confirm these findings. Identification of the relevant seasonal
risk factors will undoubtedly be important for future disease prevention
strategies.